The Collaborative Human Tissue Network is a continuation of a successful program to increase the supply and quality of human tissues to support research in cancer. The University of Alabama at Birmingham (UAB), as the Southern Division (SD) of the CHTN, has participated effectively in all CHTN operations at the national level since 1987. The policies and guidelines that have been established have resulted in a dependable source for cancer researchers of a wide range of expertly processed, well-characterized and high quality human tissues with associated histopathologic and demographic data. New challenges to biorepository operations are emerging, however. The current advances in cancer research, including the issues surrounding research into personalized medicine, have resulted in an increase in demand for tissue samples and more complex requests. Concurrently, changes in medical care, such as preoperative therapy, use of high resolution imaging instead of tissue diagnoses, as well as a changing regulatory environment are affecting tissue collections. The leadership team of the SD has taken a proactive stance to meet the future needs of cancer investigators. (1) Enhancement of operations through recruitment of additional participating sites; increased use of archival paraffin blocks for metastatic lesions and untreated primary tumors; use of novel techniques, including nitrocellulose blots, for obtaining aliquots of small tissue specimens; and development of a rapid autopsy program. These are accompanied by increased education of investigators as to use of alternative tissues (e.g., autopsy, paraffin blocks) and to specimen limitations; (2) Enhancement of quality assurance and quality control through participation in external accreditation processes; and (3) Enhancement of the ethical and regulatory stance through expansion of utilization of patient advocates. The informatics system is critical to all biorepository functions and the SD proposes development of an Investigators' IT system that utilizes new-era interoperability and linked big-data systems. It als proposes an increased emphasis on training and proficiency testing in IT systems, coupled with greater utilization of the Web for access to and training in SOPs. The SD reaffirms its commitment to the operations of the CHTN as a whole. In addition to ongoing involvement at the leadership level, it continues significant collaborative efforts with individual divisions, including supplying tissues for microarrays and beta-testing of modifications of the current IT system. Since 2008, the SD has provided 20,287 fresh, frozen and fixed human aliquots to 264 investigators. Notably, within the CHTN network it provides complex specimens including aliquots of tissue processed within 30 minutes of collection; macrodissected paraffin and frozen tissues and mRNA/DNA samples as well as detailed clinical information and follow-up to investigators. It is one of the leading providers of fresh tissue samples and body fluids and the leading provider of samples from African-American patients.